This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Y chromosome was once thought to be responsible only for turning on sex determination towards the male pathway via the testis determinant gene Sry. However, subsequent studies revealed a number of other genes located on this chromosome that are likely to encode information important for formation and function of the male gametes. The Y chromosome was once thought to be responsible only for turning on sex determination towards the male pathway via the testis determinant gene Sry. However, subsequent studies revealed a number of other genes located on this chromosome that are likely to encode information important for formation and function of the male gametes. The goal of this project is to define the roles of certain Y encoded genes. More specifically, we seek to (1) unveil the function and mechanism of action of genes encoded on the Y chromosome long arm, (2) test whether testis determinant gene Sry plays a role in sperm function;(3) define the minimum Y gene complement that is sufficient to generate gametes capable of achieving successful fertilization. This will be done through the analysis of unique mouse models lacking various parts of the Y chromosome, and use of assisted reproduction technologies (ART): intracytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF), in combination with molecular biology approaches. Deletions within the male specific region of the Y chromosome are a common genetic cause of spermatogenic failure, making men carrying affected Y chromosome a target group for infertility treatment via ART. Given the known and potential problems associated with the use of ART in humans, it is essential to continue efforts on identifying the underlying causes of infertility. Our work will advance understanding of the Y chromosome encoded genes role in spermatogenesis and sperm function and ultimately may help to combat infertility, a major health problem in U.S.A.